The invention relates to a bioerodible device for administering active ingredients, said device being intended to be inserted into a body cavity. More particularly, it relates to a bioerodible device comprising a water-soluble muco-adherent lyophilized foam and an active ingredient; a method of using such devices; and a method for manufacturing such devices. The delivery device of the present invention adheres to mucosal tissue and is accordingly particularly suitable for use in administering active ingredients to both the buccal cavity and the vaginal cavity. The delivery device is used to provide for the controlled and sustained release of an active ingredient.
Prescription and over-the-counter medications and other pharmaceutical products have traditionally been administered through oral ingestion, nasal sprays, injection and suppositories. There are disadvantages associated with each of these methods of administration.
For example, with respect to oral ingestion of a drug, many patients, including pediatric and geriatric patients, frequently have great difficulty swallowing a pill. In addition, there is often a substantial delay between the time of oral administration of a drug until it has the desired therapeutic effect in the patient's system. Generally, a drug must pass from the stomach into the small and large intestines before it will be absorbed into the patient's bloodstream. This typically takes about forty-five minutes or longer. Moreover, many drugs that are taken orally are metabolized almost immediately and thereby rendered ineffective by the patient's system before they can have the desired therapeutic effect.
Likewise, many patients also have at least some aversion to injections or suppositories. Moreover, neither of these methods are readily conducive to self-administration.
Consequently, many patients simply fail to comply with their physicians orders with respect to taking medications that are administered in these ways.
Compressed tablets or extruded thin films, including multi-layered products, that are inserted into the buccal cavity for delivering an active ingredient are known in the art. See, for example, U.S. Pat. No. 4,540,566, Davis et al. which discloses a compressed tablet comprising cellulose ether; U.S. Pat. No. 4,389,393, Schor et al., which describes a buccal delivery system consisting of a compressed tablet comprised of hydroxypropylmethylcellulose, or a mixture of methylcellulose and sodium carboxylmethylcellulose, and/or other cellulose ethers; U.S. Pat. No. Re. 33,093, issued to Schiraldi et al.; U.S. Pat. No. 4,900,552, which discloses a trilaminate film comprised of a hydratable muco-adhesive base layer, a non-adhesive reservoir layer and a water-impermeable carrier film; U.S. Pat. No. 4,900,554, issued to Yanagibashi et al., wherein there is disclosed an adhesive device containing an adhesive layer and a water insoluble or sparingly soluble backing layer; and G.B. Patent No. 2,108,841, which also discloses a multi-layered product comprising a non-adhesive layer and an adhesive layer.
However, although these devices are useful, there are also disadvantages associated with their use which renders them unsuitable for many applications and unacceptable to the patient. For example, many of these devices do not last very long. In U.S. Pat. Nos. 4,717,723 and 4,829,056, Sugden discloses a compressed tablet for dispensing prochlorperazine or etorphine (or a salt thereof), respectively. Sugden's devices are intended to remain in position and dispense a drug for up to 2 hours. Likewise, in European Patent Application No. 371,466, there is described a buccal tablet for administering estradiol that is designed to dissolve very rapidly (that is, in about one minute). Accordingly, these devices are not suitable when clinical indications require a longer release time.
Furthermore, the hardness of the devices makes them highly uncomfortable when placed in the buccal cavity. In addition, they are inconvenient to apply, bulky, and difficult to keep in place.
In the area of foams, although the use of foams and freeze-dried foams to deliver various active ingredients is well-known, such foams generally do not possess the requisite characteristics that would render them suitable for use as a muco-adherent delivery device. For example, in U.S. Pat. No. 4,642,903, Davies discloses the use of freeze-dried foams for dispensing a variety of active ingredients. However, Davies' foams are designed to have very rapid dissolution times (virtually instantaneous) which would render those foams highly ineffective for use as an active ingredient dispensing device when longer release times are required. Moreover, in Davies' foaming process it is not possible to control the degree of aeration which is critical in order to manufacture batches of devices having substantially equivalent properties. Accordingly, using Davies' method it is not possible to control the density, dosages, dosage delivery rate and dissolution time of the devices from manufactured batch to manufactured batch.
Similarly, in U.S. Pat. No. 4,292,972, Pawelchak et al. discloses a lyophilized foam sponge product containing sodium carboxylmethylcellulose, pectin, gelatin, and a pharmaceutical, that is intended primarily for use as a hemostatic agent. Unfortunately, Pawelchak's dispersions do not aerate readily; the freeze-dried foams tend to be brittle and dissolve too quickly.
Japanese patent Application No. 78-145170 describes a method for manufacturing a polyvinyl-alcohol-based sponge material intended for use as an operating sponge for hemostasis. The device is made by foaming aqueous polyvinyl alcohol solution having nonionic cellulose ethers dispersed therein, and freeze drying the foamed mixture at reduced pressure. The foams produced by this method have several disadvantages; they dissolve too rapidly, and upon lyophilization, the product is too stiff. Moreover, the method utilized to manufacture the devices suffers from the same disadvantages discussed above.
Accordingly, a need exists for a bioerodible muco-adherent delivery device that provides for the sustained and/or controlled release of an active ingredient which can be absorbed through the mucous membrane. Such a device should be convenient to insert, stay in place in the body cavity into which it is inserted, and be comfortable to wear in order to encourage the patient to self-administer the active ingredient.
Furthermore, there is a need for a method of producing such devices whereby the properties of the devices, including density, dissolution time, and active ingredient delivery rate, can be substantially controlled and readily reproduced.